Advanced coarse-grained model for fast simulation of nascent polypeptide chain dynamics within the ribosome

The nascent polypeptide exit tunnel (NPET) is a subcompartment of the ribosome that constrains the dynamics of nascent polypeptide chains during protein translation. Simulating these dynamics has been limited by the spatial scale of the ribosome and the temporal scale of elongation. Here, we present an automated pipeline to extract the geometry of the NPET and the ribosome surface at high resolution from any ribosome structure. We further convert this into a coarse-grained (CG) bead model that can be used in molecular simulations. This CG model more accurately captures NPET geometry than previous representations and allows for the simulation of co- and posttranslational processes that are computationally prohibitive with all-atom approaches. In particular, we illustrate how the CG model may be used to simulate the elongation dynamics of the nascent polypeptide and its escape posttranslation, as well as to evaluate free energy landscapes and examine the influence of electrostatics on the nascent polypeptide escape.